Gou Eric, Weng Cindy, Greene Tom, Anderson Karl E, Phillips John D
University of Texas Medical Branch, Galveston, TX.
University of Utah, Salt Lake City, UT.
J Appl Lab Med. 2018 Sep 1;3(2):213-221. doi: 10.1373/jalm.2017.025874.
Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are inherited cutaneous porphyrias resulting from decreased activity of ferrochelatase and gain-of-function mutations of δ-aminolevulinic acid synthase-2, respectively. Both of these protoporphyrias cause increased protoporphyrin levels that cause photosensitivity and may lead to hepatopathy and further increases in erythrocyte and plasma porphyrin levels.
We evaluated erythrocyte protoporphyrin and plasma porphyrin levels in all subjects with EPP (83 subjects) or XLP (9 subjects) without evidence of liver disease tested repeatedly at a single laboratory over 25 years.
Intersubject variation contributed more than intrasubject variation (78.86% vs 21.14%) to overall variability, and longitudinal variability, estimated by CV, averaged 26%. Erythrocyte total protoporphyrin levels were similar in males and females with EPP (ratio, 0.99; 95% CI, 0.82-1.21; P = 0.96) but were higher in males than females with XLP, although this difference was not statistically significant (ratio, 0.76; 95% CI, 0.43-1.36; P = 0.35). Analysis of 20 subjects from 9 separate families showed significant effects of family compared with effects of individual variation on total variance (50% vs 25%; P < 0.0001).
Variation of erythrocyte total protoporphyrin up to 25% is expected in patients with protoporphyria, whereas greater increases might raise concern for protoporphyric hepatopathy.
红细胞生成性原卟啉病（EPP）和X连锁原卟啉病（XLP）是遗传性皮肤卟啉病，分别由亚铁螯合酶活性降低和δ-氨基乙酰丙酸合酶-2功能获得性突变引起。这两种原卟啉病都会导致原卟啉水平升高，从而引起光敏感，并可能导致肝病以及红细胞和血浆卟啉水平进一步升高。
我们评估了25年间在单个实验室反复检测的所有无肝病证据的EPP患者（83例）或XLP患者（9例）的红细胞原卟啉和血浆卟啉水平。
受试者间变异对总体变异性的贡献大于受试者内变异（78.86%对21.14%），通过CV估计的纵向变异性平均为26%。EPP男性和女性的红细胞总原卟啉水平相似（比值为0.99；95%CI为0.82-1.21；P = 0.96），但XLP男性高于女性，尽管这种差异无统计学意义（比值为0.76；95%CI为0.43-1.36；P = 0.35）。对来自9个不同家庭的20名受试者的分析显示，与个体变异对总方差的影响相比，家庭影响显著（50%对25%；P < 0.0001）。
原卟啉病患者的红细胞总原卟啉预计会有高达25%的变异，而更大幅度的升高可能提示原卟啉性肝病。
